Genet Mol Biol
September 2024
The genetic architecture of complex diseases affecting populations with Indigenous American ancestries is poorly understood due to their underrepresentation in genomics studies. While most of the genetic diversity associated with disease trait variation is shared among worldwide populations, a fraction of this component is expected to be unique to each continental group, including Indigenous Americans. Here, I describe the current state of knowledge from genome-wide association studies on Indigenous populations, as well as non-Indigenous populations with partial Indigenous ancestries from the American continent, focusing on disease susceptibility and anthropometric traits.
View Article and Find Full Text PDFEarly or late pubertal onset can lead to disease in adulthood, including cancer, obesity, type 2 diabetes, metabolic disorders, bone fractures, and psychopathologies. Thus, knowing the age at which puberty is attained is crucial as it can serve as a risk factor for future diseases. Pubertal development is divided into five stages of sexual maturation in boys and girls according to the standardized Tanner scale.
View Article and Find Full Text PDFBody-mass index (BMI) is a hallmark of adiposity. In contrast with adulthood, the genetic architecture of BMI during childhood is poorly understood. The few genome-wide association studies (GWAS) on children have been performed almost exclusively in Europeans and at single ages.
View Article and Find Full Text PDFPuberty is a complex developmental process that varies considerably among individuals and populations. Genetic factors explain a large proportion of the variability of several pubertal traits. Recent genome-wide association studies (GWAS) have identified hundreds of variants involved in traits that result from body growth, like adult height.
View Article and Find Full Text PDFDetection of positive selection signatures in populations around the world is helping to uncover recent human evolutionary history as well as the genetic basis of diseases. Most human evolutionary genomic studies have been performed in European, African, and Asian populations. However, populations with Native American ancestry have been largely underrepresented.
View Article and Find Full Text PDFBackground And Objective: During cyclosporine-induced gingival overgrowth, the homeostatic balance of gingival connective tissue is disrupted leading to fibrosis. Galectins are glycan-binding proteins that can modulate a variety of cellular processes including fibrosis in several organs. Here, we study the role of galectin-8 (Gal-8) in the response of gingival connective tissue cells to cyclosporine.
View Article and Find Full Text PDFInorganic arsenic (As) is a toxic xenobiotic and carcinogen associated with severe health conditions. The urban population from the Atacama Desert in northern Chile was exposed to extremely high As levels (up to 600 µg/l) in drinking water between 1958 and 1971, leading to increased incidence of urinary bladder cancer (BC), skin cancer, kidney cancer, and coronary thrombosis decades later. Besides, the Andean Native-American ancestors of the Atacama population were previously exposed for millennia to elevated As levels in water (∼120 µg/l) for at least 5,000 years, suggesting adaptation to this selective pressure.
View Article and Find Full Text PDFBackground: Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol in high- and low-density lipoproteins (HDL and LDL). Mutations in LCAT gene causes familial LCAT deficiency, which is characterized by very low plasma HDL-cholesterol levels (Hypoalphalipoproteinemia), corneal opacity and anemia, among other lipid-related traits. Our aim is to evaluate clinical/biochemical features of a Chilean family with a proband showing clinical signs of familial LCAT deficiency, as well as to identify and assess the functional effects of LCAT mutations.
View Article and Find Full Text PDFSemaphorins and their transmembrane receptors, Plexins, are key regulators of axon guidance and development of neuronal connectivity. B-type Plexins respond to Class IV semaphorins and mediate a variety of developmental functions. Here we report that the expression of Plexin-B2 and its high-affinity ligand, Sema4C, persists in peripheral sensory neurons in adult life and is markedly increased in states of persistent pain in mice.
View Article and Find Full Text PDFNeuropathic pain is a major, intractable clinical problem and its pathophysiology is not well understood. Although recent gene expression profiling studies have enabled the identification of novel targets for pain therapy, classical study designs provide unclear results owing to the differential expression of hundreds of genes across sham and nerve-injured groups, which can be difficult to validate, particularly with respect to the specificity of pain modulation. To circumvent this, we used two outbred lines of rats, which are genetically similar except for being genetically segregated as a result of selective breeding for differences in neuropathic pain hypersensitivity.
View Article and Find Full Text PDFGalectin-8 belongs to a family of mammalian lectins that recognize glycoconjugates present on different cell surface components and modulate a variety of cellular processes. A role of Gal-8 in the immune system has been proposed based on its effects in immune cells, including T and B lymphocytes, as well as the presence of anti-Gal-8 autoantibodies in the prototypic autoimmune disease systemic lupus erythematosus (SLE). We have previously described that Gal-8 induces apoptosis in activated T cells interacting with certain β1 integrins and this effect is counteracted by the anti-Gal-8 autoantibodies.
View Article and Find Full Text PDFGalectins have been implicated in T cell homeostasis playing complementary pro-apoptotic roles. Here we show that galectin-8 (Gal-8) is a potent pro-apoptotic agent in Jurkat T cells inducing a complex phospholipase D/phosphatidic acid signaling pathway that has not been reported for any galectin before. Gal-8 increases phosphatidic signaling, which enhances the activity of both ERK1/2 and type 4 phosphodiesterases (PDE4), with a subsequent decrease in basal protein kinase A activity.
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